rs11773103

Positions:

• chr7-87192664-A-G
• chr7-87192664-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142327.2(DMTF1):​c.1495-534A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0453 in 152,318 control chromosomes in the GnomAD database, including 186 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.045 (186 hom., cov: 33)
  • Exomes 𝑓: 0.037 (0 hom.)
• Consequence: DMTF1 NM_001142327.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.830

Genes affected

DMTF1 (HGNC:14603): (cyclin D binding myb like transcription factor 1) This gene encodes a transcription factor that contains a cyclin D-binding domain, three central Myb-like repeats, and two flanking acidic transactivation domains at the N- and C-termini. The encoded protein is induced by the oncogenic Ras signaling pathway and functions as a tumor suppressor by activating the transcription of ARF and thus the ARF-p53 pathway to arrest cell growth or induce apoptosis. It also activates the transcription of aminopeptidase N and may play a role in hematopoietic cell differentiation. The transcriptional activity of this protein is regulated by binding of D-cyclins. This gene is hemizygously deleted in approximately 40% of human non-small-cell lung cancer and is a potential prognostic and gene-therapy target for non-small-cell lung cancer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMTF1	NM_001142327.2	c.1495-534A>G		intron_variant		ENST00000331242.12	NP_001135799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMTF1	ENST00000331242.12	c.1495-534A>G		intron_variant		1	NM_001142327.2	ENSP00000332171	P1

Frequencies

GnomAD3 genomes AF: 0.0453 AC: 6896 AN: 152120 Hom.: 186 Cov.: 33

Gnomad AFR AF: 0.0187

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0574

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.0245

Gnomad SAS AF: 0.0373

Gnomad FIN AF: 0.0355

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0591

Gnomad OTH AF: 0.0550

GnomAD4 exome AF: 0.0375 AC: 3 AN: 80 Hom.: 0 Cov.: 0 AF XY: 0.0455 AC XY: 2 AN XY: 44

Gnomad4 AMR exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0313

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0454 AC: 6904 AN: 152238 Hom.: 186 Cov.: 33 AF XY: 0.0440 AC XY: 3276 AN XY: 74440

Gnomad4 AFR AF: 0.0186

Gnomad4 AMR AF: 0.0573

Gnomad4 ASJ AF: 0.0764

Gnomad4 EAS AF: 0.0243

Gnomad4 SAS AF: 0.0379

Gnomad4 FIN AF: 0.0355

Gnomad4 NFE AF: 0.0592

Gnomad4 OTH AF: 0.0572

Alfa AF: 0.0544 Hom.: 300

Bravo AF: 0.0464

Asia WGS AF: 0.0290 AC: 103 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.1
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11773103; hg19: chr7-86821980;